Defects in CD4+ T cell LFA-1 integrin-dependent adhesion and proliferation protect Cd47-/- mice from EAE

J Leukoc Biol. 2017 Feb;101(2):493-505. doi: 10.1189/jlb.3A1215-546RR. Epub 2016 Dec 13.


CD47 is known to play an important role in CD4+ T cell homeostasis. We recently reported a reduction in mice deficient in the Cd47 gene (Cd47-/-) CD4+ T cell adhesion and transendothelial migration (TEM) in vivo and in vitro as a result of impaired expression of high-affinity forms of LFA-1 and VLA-4 integrins. A prior study concluded that Cd47-/- mice were resistant to experimental autoimmune encephalomyelitis (EAE) as a result of complete failure in CD4+ T cell activation after myelin oligodendrocyte glycoprotein peptide 35-55 aa (MOG35-55) immunization. As the prior EAE study was published before our report, authors could not have accounted for defects in T cell integrin function as a mechanism to protect Cd47-/- in EAE. Thus, we hypothesized that failure of T cell activation involved defects in LFA-1 and VLA-4 integrins. We confirmed that Cd47-/- mice were resistant to MOG35-55-induced EAE. Our data, however, supported a different mechanism that was not a result of failure of CD4+ T cell activation. Instead, we found that CD4+ T cells in MOG35-55-immunized Cd47-/- mice were activated, but clonal expansion contracted within 72 h after immunization. We used TCR crosslinking and mitogen activation in vitro to investigate the underlying mechanism. We found that naïve Cd47-/- CD4+ T cells exhibited a premature block in proliferation and survival because of impaired activation of LFA-1, despite effective TCR-induced activation. These results identify CD47 as an important regulator of LFA-1 and VLA-4 integrin-adhesive functions in T cell proliferation, as well as recruitment, and clarify the roles played by CD47 in MOG35-55-induced EAE.

Keywords: T lymphocytes; TCR activation; autoimmune; neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigen Presentation / drug effects
  • Antigen Presentation / immunology
  • CD28 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD47 Antigen / metabolism*
  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Chemokines / pharmacology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Female
  • Humans
  • Immunization
  • Integrin alpha4beta1 / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymph Nodes / drug effects
  • Lymph Nodes / pathology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Antibodies, Monoclonal
  • CD28 Antigens
  • CD47 Antigen
  • Chemokines
  • Integrin alpha4beta1
  • Lymphocyte Function-Associated Antigen-1
  • Myelin-Oligodendrocyte Glycoprotein
  • Receptors, Antigen, T-Cell
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1